Archives of Medical Research 36 (2005) 291–299

REVIEW ARTICLE
Diabetes and Pregnancy
Gerardo Forsbach-Sánchez, Hector E. Tamez-Peréz and Julia Vazquez-Lara
Department of Endocrinology, Hospital Dr. Ignacio Morones, Instituto Mexicano del Seguro Social, Monterrey, NL, Mexico
Received for publication November 12, 2004; accepted November 12, 2004 (04/158).

Diabetes in pregnant women is associated with an increased risk for maternal and neonatal
morbidities and remains a significant medical challenge. Fortunately, the prognosis has
changed dramatically, related to an increased clinical awareness of the potential risks for
the mother and the infant, better health care and intensive treatment strategies to maintain
the closest to normal metabolic milieu.
Diabetes and pregnancy may be divided into pregestational diabetes (women previously
diagnosed with type 1 or type 2 diabetes) and gestational diabetes defined as any glucose
intolerance detected during pregnancy that has evolved from a diagnosis associated with
the metabolic risk of type 2 diabetes to a clinical condition associated with higher risks
for maternal and perinatal morbidity. Early diagnosis of gestational diabetes is an important
step to improve outcomes and systematic or selective screening with the OGTT should
be established. Associated with the global epidemic in diabetes, pregnancy associated with
diabetes is saturating high-risk obstetric clinics and neonatal intensive care units, becoming
a heavy burden to the health care systems around the world. 쑖 2005 IMSS. Published
by Elsevier Inc.
Key Words: Diabetes mellitus, Pregnancy.

Introduction mortality, but maternal and perinatal morbidity remaining

Diabetes mellitus is the most frequent metabolic pregnancy
complication associated with an increased risk of maternal
and neonatal morbidities (1). Experience and clinical aware-
ness of the potential risks are necessary to provide ad-
equate health care for both the mother and the infant (2).
Diabetes treatment in pregnant women has remained a medi-
cal challenge until now, although the prognosis has changed
from earlier times when only diet could be provided and ma-
ternal survival was unpredictable, to the time when insulin
became available for treatment and maternal survival was the
rule (3). The ominous risk of near-term fetal death became a
medical nightmare, and before-term pregnancy interruption
was adopted to avoid it, followed by a decrease of in utero
fetal deaths, but with an increase in neonatal deaths due
to respiratory distress (4). Development of lung maturation
tests and improved perinatal care decreased the prevalence of
respiratory distress improving neonatal survival (5), showing
congenital malformations as the main cause of perinatal
Address reprint requests to: Gerardo Forsbach, M.D., Hidalgo Pte. 1801,
Col. Obispado, 64060 Monterrey, NL, México. Phone: (⫹52) (81) 8123-
2681; FAX: ⫹52 (81) 8347-2021; E-mail: gbforsbach@yahoo.com
at higher rates than in the general population (6).
Most of the early work on diabetes and pregnancy was
done on type 1 patients who became pregnant, increasing
metabolic instability. Initial work by Dr. Priscilla White
established a classification of diabetes mellitus associated
with pregnancy, based on time of evolution and the presence
of vascular damage, this being useful for pregnancy progno-
sis (7) (Table 1). At the most favorable end of the scale was
gestational diabetes and at the other end were patients with
chronic renal failure, most of them type 1 patients with ex-
tremely poor pregnancy prognosis.
The consensus on diabetes classification established type
1 and type 2 diabetes as the main groups: type 1 for insulin-
dependent diabetes associated with autoimmune pancreatic
beta-cell destruction, type 2 for non-insulin-dependent dia-
betes associated with insulin resistance, and gestational di-
abetes (GDM) defined as any glucose intolerance detected
during pregnancy (8) (Table 1). This last group of patients
requires further evaluation after pregnancy because the
group may include previously undiagnosed type 2 patients
identified at the beginning of pregnancy, and normal preg-
nant women detected during the third trimester after an oral
glucose tolerance test (OGTT). Type 1 patients usually have

0188-4409/05 $–see front matter. Copyright 쑖 2005 IMSS. Published by Elsevier Inc.
d o i : 1 0 .1 0 16 / j . a rc m e d .2 00 5 .0 3 .0 01
292 Forsbach-Sánchez et al. / Archives of Medical Research 36 (2005) 291–299
Table 1. Previous and current classification of diabetes in
pregnant women
Dr. White (data from ref. 7)
Class Fetal survival (%)
A: Chemical diabetes 100
B: Maturity onset (age ⬎20 years), duration
⬍10 years, no vascular lesions
C: Age 10–19 years at onset or 10–19 years
duration, no vascular lesions
D: Age ⬍10 years at onset or ⬎20 years
duration or calcification of vessels of legs or
hypertension or benign retinopathy
E: Calcification of pelvic arteries
F: Nephropathy
Current classification (8)
Pregestational diabetes Type 1
Pregestational diabetes Type 2
Gestational diabetes (GDM)
low or normal body mass index and diabetes usually is
present during childhood or adolescence. Meanwhile, type 2
diabetes was predominantly a disease of middle age and
older people, appearing after age 40 in obese patients. How-
ever, age of onset has decreased and its appearance in ado-
lescents and children worldwide is common, especially in
high-prevalent populations (9).
The most recent criteria reevaluation for diabetes diagno-
sis included the term of prediabetes for fasting glucose intol-
erance (fasting glucose levels 100–125 mg/dL), and glucose
intolerance for 2 h glucose levels 140–199 mg/dL. Any may
be considered GDM in pregnant women by definition (10).
GDM has evolved from a diagnosis associated with the
metabolic risk of type 2 diabetes to a clinical condition
associated with higher risks for maternal and perinatal
morbidity.
A new classification for pregnant women with diabetes
based on previous diagnosis of diabetes or pregestational
diabetes, and diabetes diagnosed during pregnancy or gesta-
tional diabetes has provided a functional division on this
subject (11). Types 1 and 2 pregestational diabetes are associ-
ated with early and late complications of pregnancy, includ-
ing metabolic complications of the newborn (2,12,13).
Meanwhile, gestational diabetes is associated with complica-
tions in the second-half term of pregnancy and with met-
abolic complications of the newborn (14). Better prenatal
care has substantially improved the rates of maternal and
perinatal morbidity in pregnant women with diabetes, al-
though it remains distinctly elevated when compared with the
general population (15). The Saint Vincent declaration in
1989 proposed to improve maternal care in diabetic women to
approximate maternal and perinatal morbidity to the general
population rates in the following years (16), but this goal has
been difficult to reach (12).
The ethnic composition of each population group has dif-
ferent rates of type 1 and type 2 diabetic patients, although
type 2 patients represent more than 80% of the world popula-
tion with diabetes; Nordic Europeans and Anglo-Saxon pop-
ulations have higher rates of type 1 diabetes (17); meanwhile,
Hispanic, Asian, and African populations have shown higher
rates of type 2 diabetes (18). In the American population,
67
Hispanic whites have a higher prevalence of diabetes than
non-Hispanic whites, and Puerto Rican and Mexican-Ameri-
48 cans have the highest rates of diabetes (19). In Mexico,
diabetes mellitus has evolved from a rare diagnosis at the
32 beginning of the 20th century to the leading cause of general
mortality in the year 2000, affecting more women than men
13 (20). Moreover, the gap between the first and the second
3 leading causes of mortality has increased in 2001 (21). Re-
cently, a nationwide survey in adults ⬎20 years disclosed
a diabetes prevalence of 8.18%. Taking into consideration
that the authors could have underestimated the prevalence
(22), this result is close to the estimated prevalence of 9.5%
of self-reported diabetes in the Hispanic group in the U.S.
(23). Moreover, an analysis of the total direct costs to provide
health care for patients with type 2 diabetes and its chief
complications in three social security health systems of
Mexico showed a 26% increase from the year 2003 to the
year 2005, demonstrating the heavy economic burden of
diabetes for the health care system (24).
Pregestational Diabetes Mellitus (PGDM)
The PGDM population composition of type 1 and type 2
diabetes varies on the basis of ethnic characteristics. Type 2
diabetes predominates in the immigrant groups of Asian and
African origin in Norway (25). In the French population,
type 1 diabetes represents two thirds and type 2, one third
(26). The American population reports two thirds of type 2
and one third of type 1 (27). However, type 2 diabetes is
predominant in Mexican-Americans (28), and the Mexican
population shows 90% of type 2 and 10% of type 1 (29).
Young women with type 2 diabetes have recently shown
association with increased obesity, even in Nordic Euro-
pean groups where type 2 diabetes in the young was a rare
event (30).
Diabetic women who desire pregnancy should be thor-
oughly evaluated before pregnancy, since long-lasting diabe-
tes induces micro- and macrovascular lesions that affect
pregnancy prognosis, mainly in type 1 patients and with
possibly a longer-lasting evolution. The preconceptional as-
sessment must include physical examination and laboratory
evaluation of lipid levels and kidney function, and an oph-
thalmologic evaluation of the retina. Additional studies to
assess peripheral pulses and cardiac tests may be necessary.
Retinal damage, if present, should be treated to avoid the
risk of progression during pregnancy (31). With these results,
treatment must be oriented to improve general metabolic
condition with tight glucose control with normal glycosyl-
ated hemoglobin levels. Pregnancy risks should be discussed
 Diabetes and Pregnancy 293

with the patient. All previously prescribed drugs should be Table 2. Maternal and perinatal complications during pregnancy
evaluated and changed, if necessary. Angiotensin-converter (2,13,14,15,40,41,49,50,56)

enzyme inhibitors and angiotensin receptor blockers are
contraindicated in pregnancy (32). Complications associated
with long-term diabetes such as chronic hypertension, mi-
croalbuminuria and diabetic nephropathy may complicate
pregnancy prognosis (15). Chronic hypertension is a major
risk for the development of superimposed preeclampsia (33).
Microalbuminuria also has been reported to be associated
with an increased rate of preeclampsia and preterm delivery
(34). Meanwhile, albuminuria is associated with more ex-
tensive renal damage, frequently evolving to a nephrotic
syndrome during pregnancy (35). In this condition protein
losses in urine are difficult to compensate for and fetal devel-
opment is usually retarded, resulting in a preterm small-for-
gestational age newborn (36). Chronic renal failure has a
poor prognosis for pregnancy, even with dialysis (37). Trans-
planted patients, however, have had successful pregnan-
cies (38).
Insulin therapy is the recommended treatment for tight
glucose control during pregnancy. Since insulin does not cross
the placental barrier, several schemes of treatment have been
proposed, using two, three or four insulin applications, or
using an insulin pump under special conditions (39). Type
1 patients are familiar with insulin therapy and related
side effects, especially hypoglycemia when tight glucose
control is stressed; meanwhile, type 2 patients usually
have been treated with diet and oral hypoglycemic drugs
(OHD) and most have never used insulin. The preconcep-
tional evaluation may be useful for them to become familiar
with insulin therapy, its potential side effects and resolution.
Recent data from controlled groups have provided sub-
stantial knowledge about expectations that may be obtained
with intensive treatment of diabetes during pregnancy. A
subgroup of type 1 patients of the Diabetes Control and
Complications Trial Research Group (DCCT), which was
designed to evaluate the effect of tight glucose control for
diabetes complications, became pregnant. They were ran-
domized to receive tight glucose control vs. conventional
treatment. The results showed that tight glucose control
during the early weeks of pregnancy reduced congenital
malformations and spontaneous abortions to the rates ob-
served in the general population; however, no other improve-
ment in maternal or neonatal complications was obtained
comparing intensive glucose control vs. conventional treat-
ment (40). The United Kingdom Preventive Diabetes Study
(UKPDS) also evaluated the effect of tight glucose control
on complications of type 2 patients. They reported on a
small group of 16 pregnancies in eight patients but only
eight ended in live births, despite tight glucose control (41).
At any rate, improving complication rates during the first
trimester of pregnancy seems to be a reliable goal (Table 2).
Unfortunately, outcome reports in the general diabetic popu-
lation have shown that even the first trimester complication
improvement obtained in the DCCT group are difficult to
First trimester (pregestational diabetes)
Spontaneous abortion
Congenital malformations
Ketoacidosisa
Hypoglycemiab
Second and third trimester (pregestational and gestational diabetes)
Ketoacidosisa
Hypoglycemiab
Albuminuria and nephrotic syndromec
Pregnancy-induced hypertension (hypertension associated with
pregnancy)
Preeclampsia
Polyhydramnios
Large-for-gestational-age fetus
Small-for-gestational-age fetus
Fetal death near term
Miscarriage
Preterm delivery
Cesarean section
Neonatal complications
Large-for-gestational age (macrosomia)
Small-for-gestational age
Preterm newborn
Congenital malformations
Respiratory distress syndrome
Hypoglycemia
Neonatal jaundice
Polycythemia
Hypocalcemia
a
Type 1 patients; bintensive insulin therapy; cpregestational diabetes patients
with microalbuminuria/albuminuria.
obtain in the general diabetic population where stillbirths
and congenital malformations occur at increased rates over
the non-diabetic population (12,13,25,26). Further analysis
of these results has shown that unplanned pregnancies and
maternal care provided by peripheral clinics are serious prob-
lems for improving outcomes (26). Diabetic women who do
not plan their pregnancies seek medical care after several
weeks of gestation. Diabetic women who plan their pregnan-
cies receive preconceptional evaluation and treatment and
have a better chance to avoid first trimester complications.
Prenatal care provided by clinics that are familiar with
diabetes treatment and complications during pregnancy have
improved outcomes.
Maternal complications in the second-half term of preg-
nancy are predominantly associated with pregnancy-induced
hypertension that occurs in 5–10% of all pregnancies in
developed and developing countries (33). It is considered
the main cause of maternal and perinatal morbidity and may
be classified as preeclampsia or as transitional gestational
hypertension (42). Preeclampsia also occurs more frequently
in diabetic mothers than in the non-diabetic pregnant woman,
and it has been suggested that pregnancy-induced hyper-
tension may be a clinical manifestation of insulin resistance
294 Forsbach-Sánchez et al. / Archives of Medical Research 36 (2005) 291–299
(IR) because normal pregnancy is an IR physiologic condi-
tion. Moreover, preeclampsia is associated with other meta-
bolic abnormalities associated with the metabolic syndrome
(MS)-like dyslipidemia and hyperuricemia (43). Polyhy-
dramnios is frequently associated with maternal diabetes but
may occur associated with congenital malformation. Exces-
sive amniotic fluid in diabetic pregnant women has been
explained as a manifestation of IR (44), although some re-
ports have challenged this observation (45). However, hyper-
insulinemia and IR are hallmarks of normal pregnancy
peaking during the third trimester, in the same manner
as preeclampsia (46). Preeclampsia is the major cause of
preterm delivery because the only effective treatment is
ending gestation. Preterm delivery defined as ⬍37 weeks of
pregnancy occurs in 11% of all pregnancies and is associated
with neonatal deaths and approximately one half of cases of
congenital neurologic disability. Births before 32 weeks
gestation account for most neonatal deaths and disorders
(47). Preterm birth and cesarean section occur at higher
rates than in the general populations as a natural consequence
of maternal and fetal complications, with the best outcome
for both the mother and the fetus (48). Frequent patient
monitoring and early detection of complications are an im-
portant part of maternal care.
Perinatal mortality in PGDM has substantially improved
during the last decades, although it remains at an in-
creased rate over the general population (49). With improved
perinatal care, congenital malformations have emerged as a
major cause of perinatal mortality in the infants of PGDM
mothers, frequently associated with hyperglycemia at the
beginning of gestation in unplanned pregnancies of patients
who did not receive preconceptional advice (50). Caudal
regression syndrome and sirenomelia have been characteris-
tically described associated with diabetes (51); however, they
are rare events. More common malformations occur at higher
rates associated with maternal diabetes (52). Of these, cardio-
vascular malformations occur with a two- to fivefold increase
compared to the non-diabetic population, being over-
represented by transposition of the great arteries, truncus
arteriosus and tricuspid atresia (53), followed by genitouri-
nary tract and musculoskeletal anomalies. Patients with
GDM are a heterogeneous group who may be mixed with type
2 patients not previously diagnosed, but excluding type 2
patients, congenital malformations occur in similar propor-
tion to the non-diabetic population (14). Unplanned pregnan-
cies in type 2 patients may be exposed to OHD that initially
were considered a teratogenic risk (54). More recent studies
have considered that hyperglycemia in the early weeks of
gestation is the most important teratogenic risk (55).
Large-for-gestational age (LGA) and macrosomic new-
born are the most common perinatal complications of preges-
tational and GDM (56,57), although they may also occur
associated with maternal obesity and excessive weight in-
crease during pregnancy (58). LGA is defined as newborn
weight ⬎90 percentile for gestational age, but macrosomia
has a controversial definition due to two criteria for diagno-
sis: 4000 g or 4500 g (59). LGA will be used here to describe
both conditions. The fetal growth spurt is apparently initiated
in the second half of pregnancy, and high maternal glucose
levels may induce fetal overgrowth. Prospective studies in
pregnant women with hyperglycemia have shown that tight
glucose control during the second and third trimester may
halt fetal overgrowth and decrease fetal weight, reducing
the risk of LGA (60). However, this goal seems difficult to
obtain since even in the DCCT group of pregnancy, the
prevalence of LGA associated with diabetes did not
change comparing conventional treatment vs. tight glucose
control, and LGA continues to be reported as the most
frequent complication of maternal diabetes in controlled and
population studies (12,13,15,25,29,56,57). Identification of
an LGA fetus before birth is very important to avoid scapular
injury or brachial plexus elongation. An LGA fetus is at risk
for other metabolic complications associated with maternal
diabetes, including near-term fetal death that seems to occur
in excess in type 2 patients (61,62), and having an engrossed
cardiac septum with ventricular dysfunction (63).
The respiratory distress syndrome of the newborn was the
leading cause of mortality when lung maturation tests
were not available and preterm delivery was routinely in-
duced (64). Currently, lung maturation tests, prenatal lung
maturation induction with cortisone, and better perinatal care
have decreased the prevalence of respiratory distress and
the neonatal mortality for this cause (65). However, new-
borns of diabetic mothers may also present other metabolic
complications in the first days of life such as neonatal jaun-
dice, hypoglycemia, polycythemia, and hypocalcemia.
These well-defined conditions occur in newborns of diabetic
mothers at higher rates than those in the general population
(49). Hypoglycemia in the newborn is associated with fetal
hyperinsulinism secondary to maternal hyperglycemia, but
even tight glucose control has not decreased its prevalence
(40,56,57). Polycythemia in the neonate may cause hyper-
viscosity syndrome with an increased risk of thrombosis.
This complication is considered secondary to intrauterine
hypoxia or hypoxic complications during labor or delivery
and is accompanied by high erythropoietin serum levels
(66). Although there is general agreement that tight maternal
glucose control is the optimal treatment, these complications
remain a heavy burden for neonatal intensive care units.
Type 2 diabetes is the most common form of diabetes in
ethnic groups with high prevalence of diabetes such as
Latin Americans, Africans, Asians and South Pacific Island-
ers. It is appearing worldwide in young people associated with
the increased rates of obesity with a large proportion of
women with PGDM (67). This same pattern has been ob-
served in the immigrant population of the U.S. where these
ethnic groups also have a high prevalence of type 2 diabetes
(18). Only recently, outcomes of pregnant type 2 patients have
been reported and analyzed, separated from type 1 patients.
Although both share the same complications of pregnancy,
 Diabetes and Pregnancy
they usually do not have secondary vascular lesions associ-
ated with diabetes. However, they are usually treated with
OHD and may have hyperglycemia in the early weeks of
gestation, especially in unplanned pregnancies, explaining
why several recent reports describe a poor pregnancy
prognosis in these patients (26,28,41,62,67,68).
Diet and OHD are the hallmarks for the treatment of type
2 diabetes; however, OHD were proscribed as treatment
during pregnancy due to the potential placental transfer to
the fetus, increasing fetal hyperinsulinism (28). Recently,
however, two OHD, glyburide (glybenclamide) and metfor-
min, have been used during pregnancy with different results
(57,69). Glyburide is a sulfonylurea that increases insulin
secretion. Studies in vitro showed that it could not cross the
placental barrier in significant amounts (70) and it was used
in two clinical randomized studies for gestational diabetes,
using it during the second trimester of pregnancy and stop-
ping it 2 weeks before delivery. The results were compared
with a group treated with insulin, finding no significant
differences in maternal and neonatal outcomes (57,71). On
the other hand, metformin is a biguanide that increases insu-
lin sensitivity and although it is widely employed for treat-
ment in type 2 patients, it was used during early pregnancy
in women with hyperandrogenism associated with polycystic
ovary syndrome (PCOS) to reduce maternal androgen secre-
tion and improve miscarriage risk (69). Although there is
scarce clinical experience, one group reported that pregnant
women treated with metformin had higher rates of pre-
eclampsia and perinatal mortality than pregnant women
treated with insulin or with sulfonylureas (72); however, a
prospective trial with GDM patients treated with metformin
is in progress in Australia (73). Use of OHD appears to
be an interesting perspective and could be an alternative
treatment for women with GDM and type 2 diabetes. Further
clinical studies must confirm their security and tolerance.
Obesity, Insulin Resistance and the Metabolic
Syndrome
Obesity is a major risk for diabetes and during the last years
has evolved worldwide in epidemic proportions succeeded
by an increase in IR and its clinical manifestations: MS,
GDM and type 2 diabetes (74). Today obesity is replacing
the most traditional public health concerns, including under-
nutrition and infectious diseases, as one of the major contri-
butions to illness. Obesity is a chronic disease affecting both
children and adults. It was defined as a body mass index
(BMI) ⬎30, while overweight was defined as a BMI of
25–29.9 (75). In the U.S., the adult adjusted prevalence
of obesity was 30% in 2000, compared to 22.9% from 1988
to 1994, including children and adolescents in Hispanic and
Afro-American populations (75). IR is now appearing in
children and adolescents manifested as the MS and type 2
diabetes (76), but IR is also the pathogenetic mechanism
295
of the PCOS and is a physiologic consequence of normal
pregnancy (46). Unfortunately, the most reliable technique
to evaluate IR is the steady state hyperinsulinemic clamp,
an invasive and expensive method not clinically applicable.
Simpler methods based on fasting glucose/insulin levels
have been described and proposed for clinical and epidemio-
logical use, such as the homeostasis model assessment
(HOMA), the fasting simultaneous glucose and insulin mea-
surement, and the quantitative insulin sensitivity check index
(QUICKI), but lack of general agreement about the use-
fulness of these indicators has precluded its routine use (77),
with the OGTT remaining as the most useful tool to indi-
rectly detect IR in the clinical setting. The National Choles-
terol Education Program Adult Treatment Panel III (ATP
III) has characterized it on the basis of hyperglycemia as an
indirect measurement of IR, because it is a simpler method
than the basal determinations of glucose and insulin (78).
The MS is also a major risk for cardiovascular disease, the
ATP III considers six major components and at least three of
them must be identified to establish the diagnosis: abdominal
obesity, atherogenic dyslipidemia, elevated blood pressure,
insulin resistance ⫹ glucose intolerance, a proinflammatory
state and a prothrombotic state (78). MS, as well as type
2 diabetes, is more frequent in Asian and Hispanic adult
populations, although it may appear in children and adoles-
cents. Clinical identification of MS is based on the finding
of at least three of the following components: abdominal
perimeter ⬎102 cm in men, ⬎88 cm in women; blood pres-
sure ⬎130/⬎85 mmHg; triglyceride level ⬎150 mg/dL;
HDL-cholesterol ⬍40 mg/dL in men and ⬍50 mg/dL in
women; and glucose ⬎110 mg/dL (78).
PCOS is the most common endocrine problem in women
of reproductive age affecting approximately 7% of this popu-
lation, classically described by the clinical characteristics of
obesity, hyperandrogenism, anovulation, and multiple ovar-
ian cysts (79). These clinical characteristics are accompanied
by IR, and it has been proposed that IR is also the etiologic
factor for hyperandrogenism. Moreover, hyperandrogenism
suppression does not decrease IR, but IR suppression reduces
hyperandrogenism (80). PCOS is a clinical condition of
young women associated with MS and type 2 diabetes.
Gestational Diabetes (GDM)
GDM has been defined as any glucose intolerance detected
during pregnancy. This wide definition includes type 2 pa-
tients diagnosed as GDM at the beginning of pregnancy
and normal pregnant women detected by an OGTT in the
third trimester of pregnancy (8). The main risks for develop-
ment of GDM and type 2 diabetes are obesity, belonging to
a high-prevalence ethnic group, family history of first-degree
relatives with diabetes, age ⬎25 years, previous LGA new-
born and previous GDM (8). Women who develop GDM
also have an increased prevalence of obesity and the MS and
296 Forsbach-Sánchez et al. / Archives of Medical Research 36 (2005) 291–299
an increased rate of complications during the second-half
term of pregnancy (14). Although spontaneous abortions
and congenital malformations are not increased, they may
appear in higher proportions than in the general population
if type 2 patients are included, as it may occur when hyper-
glycemia is detected during the first weeks of pregnancy (81).
The proportion of GDM patients in the pregnant diabetic
population varies among different ethnic groups. In the U.S.,
GDM comprises more than 80%, but in Mexico it comprises
only 50% of pregnant women with diabetes (27,29). GDM
may be diagnosed in pregnant women if they develop clinical
manifestations of diabetes with severe hyperglycemia (⬎200
mg/dL), confirming hyperglycemia in a second sample, or
if they have fasting hyperglycemia ⬎126 mg/dL on at least
two occasions, or if they have a diagnostic OGTT (82).
Systematic application of the OGTT to normal pregnant
women in the third trimester has been recommended to
detect GDM in ethnic groups of high prevalence and a selec-
tive screening in women with low risk for diabetes (82).
Two procedures have been proposed for GDM detection in the
third trimester of pregnancy, one endorsed by the American
Diabetes Association (ADA), which is a two-step approach
(82), and the other endorsed by the World Health Organization
(WHO), which is a one-step approach (83). The ADA proce-
dure is based on the early studies of O’Sullivan and Mahan
(84) and in summary consists of a screening test with a 50-g
glucose load and a glucose sample taken 1 h later. There
are two criteria for this result: ⬍130 mg/dL (O’Sullivan) or
⬍140 mg/dL (ADA). If this limit is exceeded, a 100-g
glucose challenge test is performed, taking samples before
the glucose load and at 1, 2 and 3 h afterwards. There are two
criteria for interpretation of these results, the National Diabe-
tes Data Group (1), and the Carpenter and Coustan (85)
(Table 3). The result is diagnostic of GDM if at least two
points are met or exceeded. The WHO approach is simpler
to perform, less expensive and is especially convenient when
financial resources are scarce and the ethnic characteristics
of the population are associated with high rates of type 2
diabetes. The WHO recommends the same OGTT in preg-
nant and non-pregnant adults that consists of a glucose load
of 75 g and a blood sample 2 h later (84). The criterion for
diagnosis of GDM is ⬎140 mg/dL, because any glucose
Table 3. Interpretation criteria for the 100 g oral glucose tolerance test
(OGTT)
National Diabetes Carpenter and
Data Group (NDDG) (1) Coustan (85)
Time (h) Venous blood Venous plasma Venous plasma
0 90 105 90
1 170 190 180
2 145 165 155
3 125 145 140
Note: All values expressed in mg/dL.
intolerance detected during pregnancy is diagnostic for
GDM (82).
GDM and type 2 diabetes are clinical manifestations of
IR. Patients who experience GDM tend to develop type 2
diabetes in the following years (81), making this group a
target for primary prevention of type 2 diabetes. The U.S.
Hispanic population is characterized by an elevated preva-
lence of diabetes, and the Mexican-American group has
one of the highest prevalence of diabetes in the Hispanic
population (86). A recent report of Mexican-Americans
found 6.8% of GDM (87), similar to previous results ob-
tained in Mexico (4.3–6.2%) using the 3-h OGTT (88). The
report also described 5.1% of patients who had one abnormal
point in the test and these patients had an increased rate of
LGA infants, showing a total of 11.9% of patients with
glucose abnormalities (87). On the other hand, the LGA
newborn is a frequent complication of GDM and has been
taken as an end point to evaluate pregnancy-related hypergly-
cemia. Several authors have compared patients who have
one abnormal point with pregnant women who had a normal
OGTT, finding higher rates of LGA infants in the former
group. They have called this abnormality impaired glucose
tolerance (87,89,90). Moreover, other authors have com-
pared LGA infant rates in pregnant women with a normal
50-g screening test vs. pregnant women with an abnormal
screening test but a normal OGTT, reporting increased rates
of LGA newborns in patients who had an abnormal screening
test (91–93). This suggests that mild maternal hyperglycemia
is a risk for the fetus (94). The LGA fetus is at risk of
obstetric trauma and of the metabolic complications of the
newborn, including near-term fetal death (95). Diet therapy
is the initial approach to control glucose and insulin therapy is
prescribed if glucose control is not achieved. Tight glucose
control has successfully stopped fetal overgrowth; however,
severe hypoglycemic episodes remain as a risk of intensive
insulin therapy (60). A novel approach for women with
GDM has suggested selecting patients at high risk for a LGA
infant, based on ultrasound measurements of the abdominal
circumference of the fetus at 29–33 weeks of pregnancy,
and submitting to insulin therapy only those over the 75th
percentile (96).
The WHO procedure is a simpler, one-step approach to
detect glucose alterations. Applying this approach in the
Mexican population, the prevalence of GDM was 16.4%
(97). GDM has evolved from a diagnosis associated with
the metabolic risk of type 2 diabetes to a clinical condition
associated with higher risks for maternal and perinatal com-
plications, because preeclampsia, preterm delivery, cesarean
sections and the metabolic complications of the newborn
occur at higher rates than in the non-diabetic population
(98–100). However, a controversial point that remains to
be elucidated is whether congenital malformations occur at
higher rates in GDM than in the non-diabetic population
because glucose abnormalities peak in the third trimester of
pregnancy (81,94,98,101).
 Diabetes and Pregnancy
In conclusion, diabetes and pregnancy may be divided
in PGDM diabetes, types 1 and 2, and GDM. The composi-
tion of the population with PGDM varies among the different
ethnic groups. Populations with a high prevalence of diabetes
have a high rate of GDM and type 2 diabetes. Women with
PGDM should be thoroughly evaluated and submitted to
tight glucose control before pregnancy. Tight glucose control
in type 1 patients has normalized spontaneous abortions and
congenital malformations but has not improved the rate of
maternal complications of the second-half term of preg-
nancy, or the metabolic complications of the newborn. Type
2 patients have had an uncertain pregnancy prognosis, and
in the small UKPDS group only 50% of pregnancies ended in
a live birth. Others authors have had similar experiences and
have documented excess of late fetal deaths. Close obstetrical
and metabolic surveillance is an important part of mater-
nal care and an experienced pediatric team is required to
assist the newborn. Type 2 diabetes and GDM are following
the worldwide epidemic of obesity that is affecting children
and adolescents. GDM is a heterogeneous group that may
include type 2 diabetes not previously identified and is asso-
ciated with the second-half term of pregnancy complications
and to the metabolic complications of the infant. Early diag-
nosis of GDM is an important step to improve outcomes
and systematic or selective screening with the OGTT of
normal pregnant women should be established, using either
the ADA or the WHO approach. If diagnosis is established,
dietary management should be the first step to control glu-
cose, and insulin therapy must be added if necessary. Careful
selection of patients at high risk for LGA fetus may choose
those patients who require intensive insulin therapy. Preg-
nancy associated with diabetes is saturating high-risk obstet-
ric clinics and neonatal intensive care units, becoming a
heavy burden to the health systems worldwide. Women who
develop GDM should be the target for primary prevention
of type 2 diabetes.
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